title: Troponin I and C-reactive protein are commonly detected in patients with breast cancer treated with dose-dense chemotherapy incorporating trastuzumab and lapatinib.
abstract: OBJECTIVE
  There are no validated methods of early detection of cardiotoxicity from trastuzumab (T) following anthracycline-based chemotherapy. Currently changes in left ventricular ejection fraction (LVEF) are assessed but this approach has limited sensitivity and specificity. Within a prospective feasibility study of dose-dense (dd) doxorubicin and cyclophosphamide (AC) → weekly paclitaxel (P) with T and lapatinib (L), we included a preplanned analysis of correlative cardiac Troponin I (cTnI) and C-reactive protein (CRP) as early biomarkers of cardiotoxicity.
  
  
  METHODS
  As previously described, patients received ddACx 4 → PTL → TL. LVEF was assessed at months 0, 2, 6, 9, and 18 and cTnI and CRP measured every 2 weeks during chemotherapy then at months 6, 9, and 18. These biomarkers were correlated with changes in LVEF.
  
  
  RESULTS
  Ninety-five patients enrolled. Overall, 3 (3%) patients withdrew during AC and 41 (43%) withdrew during PTL → TL, mostly due to diarrhea. Median LVEF was 68% (baseline), 69% (month 2), 65% (month 6), 65% (month 9), and 65% (month 18). The majority (67%) had a detectable cTnI during the study. The proportion of detectable cTnIs increased over time; 4% at baseline, 11% at month 2, and 50% at month 3. The timing of these detectable cTnIs preceded maximum-recorded decline in LVEF. However, overall, maximum cTnI levels did not correlate with LVEF declines. A detectable CRP was seen in 74/95 (78%) but did not correlate with LVEF declines.
  
  
  CONCLUSIONS
  In patients receiving ddAC → PTL, cTnIs are commonly detected. These elevations may precede changes in LVEF but, as assessed in this trial, do not predict CHF.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA. morrisp1@mskcc.org
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Morris
authors.forename: Carol
authors.initials: C
authors.lastname: Chen
authors.forename: Richard
authors.initials: R
authors.lastname: Steingart
authors.forename: Martin
authors.initials: M
authors.lastname: Fleisher
authors.forename: Nancy
authors.initials: N
authors.lastname: Lin
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.forename: Steven
authors.initials: S
authors.lastname: Come
authors.forename: Steven
authors.initials: S
authors.lastname: Sugarman
authors.forename: Alyson
authors.initials: A
authors.lastname: Abbruzzi
authors.forename: Robert
authors.initials: R
authors.lastname: Lehman
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.forename: Maura
authors.initials: M
authors.lastname: Dickler
authors.forename: Heather L
authors.initials: HL
authors.lastname: McArthur
authors.forename: Eric
authors.initials: E
authors.lastname: Winer
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Chau T
authors.initials: CT
authors.lastname: Dang
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D013318:Stroke Volume / Q000187:drug effects; D000068878:Trastuzumab; D019210:Troponin I / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D011799:Quinazolines; D019210:Troponin I; D000077341:Lapatinib; D002097:C-Reactive Protein; D000068878:Trastuzumab